Histopathology is required to identify and characterize myopathies in high-throughput phenotype screening of genetically engineered mice.
Vet Pathol
; 58(6): 1158-1171, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34269122
ABSTRACT
The development of mouse models that replicate the genetic and pathological features of human disease is important in preclinical research because these types of models enable the completion of meaningful pharmacokinetic, safety, and efficacy studies. Numerous relevant mouse models of human disease have been discovered in high-throughput screening programs, but there are important specific phenotypes revealed by histopathology that are not reliably detected by any other physiological or behavioral screening tests. As part of comprehensive phenotypic analyses of over 4000 knockout (KO) mice, histopathology identified 12 lines of KO mice with lesions indicative of an autosomal recessive myopathy. This report includes a brief summary of histological and other findings in these 12 lines. Notably, the inverted screen test detected muscle weakness in only 4 of these 12 lines (Scyl1, Plpp7, Chkb, and Asnsd1), all 4 of which have been previously recognized and published. In contrast, 6 of 8 KO lines showing negative or inconclusive findings on the inverted screen test (Plppr2, Pnpla7, Tenm1, Srpk3, Sidt2, Yif1b, Mrs2, and Pnpla2) had not been previously identified as having myopathies. These findings support the need to include histopathology in phenotype screening protocols in order to identify novel genetic myopathies that are not clinically evident or not detected by the inverted screen test.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças dos Roedores
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Proteínas de Transporte de Nucleotídeos
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Doenças Musculares
Tipo de estudo:
Diagnostic_studies
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Guideline
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Prognostic_studies
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Screening_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article